Resistance is cheap
Antimicrobial resistance doesn’t always cost bacteria, which will hinder our efforts to tackle this problem.
The fluoroquinolones are a group of antimicrobials that are used to treat a variety of life-threatening bacterial infections, including typhoid fever. Before the introduction of antimicrobials, the mortality rate from typhoid fever was 10–20%. Prompt treatment with fluoroquinolones has reduced this to less than 1%, and has also decreased the severity of symptoms suffered by people with the disease.
Now, however, the usefulness of many antimicrobials, including the fluoroquinolones, is threatened by the evolution of antimicrobial resistance within the bacterial populations being treated. Drug resistance in bacteria typically arises through specific mutations, or following the acquisition of antimicrobial resistance genes from other bacteria. It is thought that the frequent use of antimicrobials in human and animal health puts selective pressure on bacterial populations, allowing bacterial strains with mutations or genes that confer antimicrobial resistance to survive, while bacterial strains that are sensitive to the antimicrobials die out.
At first it was thought that specific mutations conferring antimicrobial resistance came at a fitness cost, which would mean that such mutations would be rare in the absence of antimicrobials. Now, based on research into typhoid fever, Steve Baker and co-workers describe a system in which the majority of evolutionary routes to drug resistance are marked by significant fitness benefits, even in the absence of antimicrobial exposure.
Typhoid is caused by a bacterial pathogen known as Salmonella Typhi, and mutations in two genes — gyrA and parC — result in resistance to fluoroquinolones. Baker and co-workers show that mutations in these genes confer a measurable fitness advantage over strains without these mutations, even in the absence of exposure to fluoroquinolones. Moreover, strains with two mutations in one of these genes exhibited a higher than predicted fitness, suggesting that there is a synergistic interaction between the two mutations. This work challenges the dogma that antimicrobial resistant organisms have a fitness disadvantage in the absence of antimicrobials, and suggests that increasing resistance to the fluoroquinolones is not solely driven by excessive use of this important group of drugs.
To find out more
Listen to Steve Baker talk about antibiotic resistance in episode 7 of the eLife podcast.
Read the eLife research paper on which this eLife Digest is based: “Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure” (December 10, 2013).
Read a commentary on this research paper: “Antimicrobial resistance: Fitness gains hamper efforts to tackle drug resistance”.
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